Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.5.4.4 (adenosine deaminase)
5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Orthodromically and antidromically evoked field potentials, as well as changes in the extracellular calcium concentration [Ca2+]o were measured with ion selective/reference electrodes in area CA1 of rat hippocampal slices. Synaptic transmission was blocked by a low calcium, high magnesium medium. After cutting through the alveus, stratum pyramidale (Spyr) and part of stratum radiatum (Srad), repetitive electrical stimulation of Schaffer collaterals and commissural fibers elicited decreases of [Ca2+]o in Srad, the synaptic area, but not in Spyr, the soma layer of the pyramidal neurons. This indicates the absence of a measurable somatic Ca2+ influx due to postsynaptic activation and therefore, the decrease of [Ca2+]o in Scrad presumably reflect presynaptic Ca2+ entry. Antagonists of adenosine action such as adenosine deaminase and theophylline had no effects Ca2+ entry whereas 4-AP enhanced calcium signals in Scrad considerably. In some cases small [Ca2+]o decreases in Spyr appeared after treatment with 4-AP although field potentials did not reveal postsynaptic components. When 4-AP and antagonists of adenosine action were combined, a partial recovery of synaptic transmission was consistently seen during the course of repetitive stimulation. This was indicated by large decreases of [Ca2+]o in Spyr as well as by the generation of postsynaptic field potentials. The latter appeared late during the train pointing to frequency potentiation and a presynaptic site of action. The findings indicate that physiological levels of adenosine in the order of 1 microM have a powerful modulatory role on synaptic transmission by depressing presynaptic transmitter release. This seems to result not from an influence on presynaptic calcium uptake, but rather from changing the intracellular level of calcium or its coupling to the secretory process.
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PMID:Adenosine antagonists combined with 4-aminopyridine cause partial recovery of synaptic transmission in low Ca media. 283 16

We examined the mechanism by which adenosine inhibits prolactin secretion from GH3 cells, a rat pituitary tumour line. Prolactin release is enhanced by vasoactive intestinal peptide (VIP), which increases cyclic AMP, and by thyrotropin-releasing hormone (TRH), which increases inositol phosphates (IPx). Analogues of adenosine decreased prolactin release, VIP-stimulated cyclic AMP accumulation and TRH-stimulated inositol phospholipid hydrolysis and IPx generation. Inhibition of InsP3 production by R-N6-phenylisopropyladenosine (R-PIA) was rapid (15 s) and was not affected by the addition of forskolin or the removal of external Ca2+. Addition of adenosine deaminase or the potent adenosine-receptor antagonist, BW-A1433U, enhanced the accumulation of cyclic AMP by VIP, indicating that endogenously produced adenosine tonically inhibits adenylate cyclase. The potency order of adenosine analogues for inhibition of cyclic AMP and IPx responses (measured in the presence of adenosine deaminase) was N6-cyclopentyladenosine greater than R-PIA greater than 5'-N-ethylcarboxamidoadenosine. This rank order indicates that inhibitions of both cyclic AMP and InsP3 production are mediated by adenosine A1 receptors. Responses to R-PIA were blocked by BW-A1433U (1 microM) or by pretreatment of cells with pertussis toxin. A greater amount of toxin was required to eliminate the effect of R-PIA on inositol phosphate than on cyclic AMP accumulation. These data indicate that adenosine, in addition to inhibiting cyclic AMP accumulation, decreases IPx production in GH3 cells, possibly by directly inhibiting phosphoinositide hydrolysis.
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PMID:Regulation of GH3-cell function via adenosine A1 receptors. Inhibition of prolactin release, cyclic AMP production and inositol phosphate generation. 284 12

Rat hippocampal slices were superfused with low calcium, high magnesium medium. Reductions in flow rate were associated with a marked depression of antidromically elicited afterpotentials with little change in the initial antidromic population spike recorded from CA1 pyramidal neurons. The depression of the afterpotential at the lower flow rates was largely reversed by the adenosine antagonist, theophylline (100 microM), by adenosine deaminase (10 micrograms/ml) and was mimicked by the application of the adenosine reuptake blocker, dipyridamole (100 microM). Since synaptic transmission was blocked, it is concluded that sufficient endogenous adenosine exists in the absence of synaptic function to alter neuronal excitability.
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PMID:Modulation of neuronal excitability by endogenous adenosine in the absence of synaptic transmission. 284 14

Cyclic AMP has been implicated as a regulator of capacitation, but the control of its metabolism in sperm remains obscure. A recent study of mouse sperm has shown capacitation-related changes in the activities of both adenylate cyclase, which increased during incubation, and cyclic nucleotide phosphodiesterase, which decreased. The present study was conducted to extend these observations by measuring phosphodiesterase activity in sperm incubated in media with modified calcium and/or glucose content, conditions known to modulate fertilizing ability. Phosphodiesterase activity of sequential sperm samples, taken first when sperm are essentially uncapacitated and then when they are either partially or completely capacitated, decreased with time under all conditions, and in each case the greater fall in activity was seen in the medium that would support the greater change in fertilizing ability of the sperm population. Sperm washed by centrifugation to remove epididymal fluid also displayed a reduction in phosphodiesterase activity with time. The medium surrounding the sperm contained about half of the total phosphodiesterase activity, as well as 5'-nucleotidase and adenosine deaminase. The crude enzyme preparation showed complex kinetic behavior when assayed over a range of cAMP concentrations, but the reduction in activity with time was seen at all substrate levels. The observed changes in phosphodiesterase activity, together with the increased adenylate cyclase activity seen under these sperm incubation conditions, would increase cAMP availability with time, thus providing further evidence for a fundamental role for cAMP in controlling the events of capacitation.
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PMID:Phosphodiesterase activity of mouse sperm incubated under conditions that modulate fertilizing potential in vitro. 285 27

The effects of L-glutamate and other dicarboxylic amino acids on the accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in slices of cerebral cortex from strain 2 guinea pigs were examined using tissue from animals at 39 days gestation to 7 days after birth. Responses to glutamate were inhibited completely by adenosine deaminase or theophylline unless histamine was present. When tested in the presence of adenosine, glutamate increased cyclic AMP accumulation up to 10-fold at 39 days gestation; the response was maximal at 52 days gestation, and both the efficacy and potency of glutamate declined thereafter. While the effects of glutamate were smaller in the presence of histamine plus theophylline, the developmental pattern was similar to that in the presence of adenosine. The relative potencies of D-aspartate, kainate, and alpha-methyl-DL-glutamate were much greater in fetal than in adult tissue. Glutamic acid diethyl ester, N-acetyl glutamate or 2,3-diaminopropionate had no effect in fetal tissue either in the presence or absence of glutamate. Responses to glutamate in adult tissue were much more dependent upon the presence of calcium ions than were those in fetal tissue. It was concluded that responses to glutamate involve mechanisms that differ in fetal and adult tissue.
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PMID:Ontogeny of adenosine 3',5'-monophosphate metabolism in guinea pig cerebral cortex. II. Development of responses to L-glutamate in the presence of adenosine or histamine. 288 13

ATL is a unique T-cell malignancy first described by Takatsuki and colleagues in 1970s. We estimate that more than 300 patients a year have been detected in the endemic areas of Kyushu, Japan. The surface phenotype of ATL cells characterized by monoclonal antibodies is T3+, T4+, T8-, T11+ and Tac+. In all cases the serum is positive for anti-HTLV-I antibodies and the ATL cells contain the proviral DNA of HTLV-I. Variations in the clinical features of atypical ATL suggested a division of the spectrum of ATL into five types: acute; chronic; smoldering; crisis; and lymphoma. Typical ATL takes an acute course. The survival time is short, with 50% mortality within approximately 5 months. In general a poor prognosis is indicated by the elevation of serum lactate dehydrogenase, calcium, and bilirubin, as well as by high WBC. Smoldering ATL is characterized by the presence of a few abnormal cells (0.5%-3%) in the peripheral blood over a long period. Crisis in chronic or smoldering ATL means the progression of the disease to acute ATL. The lymphoma type of ATL is considered to be a form of T-cell-type non-Hodgkin's lymphoma in which malignant cells contain proviral DNA of HTLV-I. Screening of the sera from healthy adults for presence of the anti-HTLV-I antibodies revealed that 3.6% of healthy individuals in Kumamoto Prefecture, which is located in the middle of Kyushu, were HTLV-I carriers. Family studies showed that the routes of natural infection of HTLV-I are from mother to child and also from husband to wife. The borderline between the healthy carrier state and smoldering ATL remains unclear. Smoldering ATL is frequently diagnosed in patients with fungus infection of the skin, chronic lymphadenopathy, interstitial pneumonitis, chronic renal failure and strongyloidiasis. Five patients with ATL refractory to conventional chemotherapeutic agents were treated with 2'-deoxy-coformycin (DCF), a potent inhibitor of adenosine deaminase. Two patients showed a good response, and three were resistant to DCF. In addition our experiences with a concurrence of lymphoma-type ATL in three sisters and spontaneous remissions in a patients with chronic ATL will be referred.
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PMID:[Overview of ATL (adult T-cell leukemia) research]. 288 29

Alkylxanthine drugs, such as theophylline, block adenosine receptors, inhibit phosphodiesterases and other enzymes, and cause the release of calcium from intracellular stores. Adenosine receptor blockade occurs at low micromolar concentrations of the drugs, while other effects occur in the millimolar concentration range. The effects of theophylline were tested on spontaneous transmitter release at the frog cutaneous-pectoris neuromuscular junction (NMJ). A change in the frequency, but not the amplitude, of miniature endplate potentials (mepps) was interpreted as a change in spontaneous transmitter release. In normal Ringer's, theophylline, at concentrations of 100 microM and 1 mM, theophylline had no consistent effect on spontaneous release. In contrast, theophylline produced dual effects on mepp frequency in hyperosmotic Ringer's. At 10 microM, theophylline depressed mepp frequency, while, at 100 microM and 1 mM, theophylline increased mepp rate. Since low micromolar concentrations of theophylline depressed spontaneous transmitter release, this action may result from adenosine receptor blockade and inhibition of a tonic, stimulatory effect of adenosine. This hypothesis was supported by the following experimental results: (1) Micromolar concentrations of theophylline reversed the effects of applied adenosine on neuromuscular transmission. (2) The inhibitory effect of theophylline was mimicked by 2 other alkylxanthines, 8-phenyltheophylline and 8-p-sulfophenyltheophylline. These drugs may be more specific adenosine receptor antagonists than theophylline. (3) The inhibitory effect of theophylline was mimicked by adenosine deaminase, an enzyme that breaks down and inactivates adenosine. (4) The depressant action of theophylline was masked by the addition of adenosine deaminase to the hyperosmotic Ringer's. Application of adenosine to the frog NMJ reduces spontaneous transmitter output.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dual effects of theophylline on spontaneous transmitter release from frog motor nerve terminals. 290 89

Slices of rabbit hippocampus were preincubated with [3H]serotonin then superfused continuously and stimulated twice electrically. The stimulation-evoked overflow of tritium was Ca2+-dependent, tetrodotoxin-sensitive and subject to modulation by serotonin autoreceptors. It was decreased by various adenosine receptor agonists in an order of potency that was typical for A1-(Ri-) receptors: N6-cyclohexyladenosine greater than (-)N6-phenylisopropyladenosine greater than 5'-N-ethylcarboxamideadenosine greater than (+)N6-phenylisopropyladenosine = adenosine. The effects of the agonists were antagonized by 8-phenyltheophylline. The hypothesis that endogenous adenosine influences hippocampal serotonin release is supported by the following findings: both the adenosine receptor antagonists (theophylline or 8-phenyltheophylline (10 microM, each)) and the enzyme adenosine deaminase (10 micrograms/ml) increased, whereas R-E 244 (3 microM), an inhibitor of adenosine uptake, significantly decreased the evoked tritium overflow. When 8-phenyltheophylline was present throughout superfusion the effects of both R-E 244 and exogenous adenosine deaminase were abolished. It is concluded that serotonin release in the rabbit hippocampus is depressed by endogenous adenosine via A1-(Ri-) receptors.
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PMID:Modulation of hippocampal serotonin (5-HT) release by endogenous adenosine. 298 5

The adenosine-sensitive cyclic AMP phosphodiesterase of rat adipocytes was found to reside in the same subcellular fraction as the enzyme sensitive to insulin. There were several similarities between the action of adenosine and that of insulin on the enzyme. The action of adenosine on the phosphodiesterase is probably like that of insulin, both being receptor-mediated, although different sites or different receptors could be involved. Adenosine analogues with intact ribose but a modified purine moiety elicited a response similar to that of adenosine. Added Ca2+ was also not a requirement for the action of adenosine. The action of adenosine was not synergistic with that of insulin, neither was adenosine essential for insulin action. Insulin stimulated the enzyme even at low cell concentrations and in the presence of adenosine deaminase. Adenosine, however, enhanced the effect of insulin, but only at insulin concentrations that produced submaximal effects. Thus the mechanisms of action could be similar or related. The time-course effect of a suboptimal concentration of insulin was transitory, like that of adenosine, and was influenced by the presence of adenosine, whereas that of a maximally effective concentration of insulin was sustained for at least 20 min and was not affected by the presence of adenosine. Isoprenaline enhanced phosphodiesterase activity stimulated by optimal concentrations of either adenosine or insulin, suggesting that their effects were mediated through different mechanisms of action.
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PMID:The action of adenosine in relation to that of insulin on the low-Km cyclic AMP phosphodiesterase in rat adipocytes. 298 6

Calcium entry blocking activities of adenosine and its potentiating compounds (dipyridamole, lidoflazine and dilazep) were studied in potassium (100 mmol/l) depolarized, dog, large coronary artery strips, in comparison to nifedipine, verapamil and diltiazem. Apparent pA2 values were calculated by using concentration-response curves for calcium before and 30 min after the addition of each dilator drug. The order of potency (using both pA2 and IC50 values) for the calcium entry blocking effect was: nifedipine greater than verapamil greater than diltiazem greater than lidoflazine greater than dilazep. Dipyridamole and adenosine had negligible calcium entry blocking activities (about 10,000 times less potent than verapamil). The calcium entry blocking activity of verapamil (using pA2 values) was 39.8 times less potent than nifedipine, and 3.6, 21.4 and 97.7 times more potent than diltiazem, lidoflazine and dilazep, respectively. The maximum relaxations induced by adenosine (3.7 X 10(-4) mol/l) and dipyridamole (5 X 10(-5) mol/l) were less than 20% that of 3 X 10(-4) mol/l papaverine. However, the other test drugs caused 80-90% relaxation under similar conditions. The relaxing effect of adenosine was inhibited by 8-phenyltheophylline (adenosine receptor antagonist) and potentiated by EHNA (an adenosine deaminase inhibitor), while dilazep-induced relaxation was not affected by these drugs. These findings suggest that the calcium entry blocking effect of dilazep in dog, large coronary artery strips is not mediated through adenosine.
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PMID:Calcium entry blocking activity of dilazep in dog coronary artery. 301 2


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